Tandem mass spectrometry, or mass spectrometry/mass spectrometry (MS/MS) may be used for complex mixture analysis due to its high specificity, wide applicability, and good sensitivity. MS/MS can be applied directly to a mixture or in conjunction with an on-line separation technique, such as gas chromatography (i.e., GC/MS/MS) or liquid chromatography (i.e., LC/MS/MS).
Ideally, each mixture component gives rise to a single ion type that is related to the component mass. Multiple peaks per mixture component can reduce sensitivity and compromise specificity, particularly when the mixture subjected to ionization is complex. Such a scenario can occur, for example, in the analysis of complex mixtures derived from biological fluids. Positive electrospray ionization of drugs and drug metabolites, which is a common approach for non-volatile analytes, either in conjunction with LC or flow injection, may lead to multiple ion types per component. This may be particularly common with solutions having a relatively high salt content.
The ion types generally include the protonated molecule and the analyte molecule with one or more excess metal ions that may originate from the sample matrix (sodium and potassium ions being most common). This phenomenon gives rise to an undesirable distribution of analytical signal among the various distinct ions, more complex spectra, and possible ambiguities in the masses of the mixture components because the identities of ion types are may not be obvious.